title: Critical role of matrix metalloproteinase-9 in acute cold exposure-induced stroke in renovascular hypertensive rats.
abstract: Our objectives are to investigate the role of MMP-9 in cold exposure-induced stroke and assess the preventive effect of doxycycline, a total of 200 rats were assigned to a control group, sham group, 2-kidney, 2-clip (2K-2C) group, and doxycycline-received 2K-2C group (2K-2C+doxy) (N=50, each), and subsequently, each group were randomly assigned to 2 groups: acute cold exposure (ACE) and nonacute cold exposure (NACE) (N=25, each). After the blood pressure was stabilized, rats were maintained on a 12-h light (22°C)/dark (4°C) cycle (ACE group) or a 12-h light (22°C)/dark (22°C) cycle (NACE group) for 3 cycles. The results showed that ACE upregulated Ang II and MMP-9 protein levels in brains and aortas and considerably enhanced stroke incidence in 2K-2C rats. In contrast, doxycycline treatment prevented upregulation of MMP-9 protein expression and activity in brains and aortas in response to ACE and significantly decreased stroke incidence. These findings suggest that cold exposure-induced MMP-9 via activation of RAS might play a critical role in the initiation of cold exposure-induced stroke during chronic hypertension and doxycycline shows protective effects against cold exposure-induced stroke.
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Li
authors.forename: Xiangpen
authors.initials: X
authors.lastname: Li
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Shen
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Yamei
authors.initials: Y
authors.lastname: Tang
authors.forename: Yidong
authors.initials: Y
authors.lastname: Wang
authors.forename: Qingyu
authors.initials: Q
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000150:complications* / Q000503:physiopathology; D007036:Hypothermia, Induced / Q000009:adverse effects*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D020521:Stroke / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D000804:Angiotensin II; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D004318:Doxycycline
keywords: 2-kidney–2-clip hypertension; Matrix metalloproteinase-9; cold exposure; doxycycline; stroke